In Reply: Dr DiNicolantonio and colleagues suggest that reverse causation may be responsible for an overestimation of the risk of bleeding in individuals treated with aspirin. The increased risk of bleeding associated with the use of aspirin has been documented in many RCTs and observational studies.1 The Antithrombotic Trialists' meta-analysis of randomized trials2 shows a 54% increase in the risk of major bleeding associated with aspirin use, consistent with our findings. DiNicolantonio et al also suggest that the increased risk of bleeding among aspirin users may be partially attributable to use of over-the-counter NSAIDs. While long-term use of NSAIDs was considered in the propensity score matching, we were unable to adjust for its use.